Production of isomenthol isomers



n t d ta es a en 3,405,185 Patented Oct. 8, 1968.

3,405,185 PRODUCTION OF ISOMENTHOL 'ISOMERS William J. Houlihan,Mountain Lakes, and Donald R.

Moore, Washington Township, N.J., assignors to Universal Oil ProductsCompany, Des Plaiues, Ill.-,-a corporation of Delaware vNo Drawing.Continuation-impart of application Ser. No. 142,770, Oct. 4, 1961. Thisapplication May 18, 1965, Ser. No. 456,803

2 Claims. (Cl. 260-631) Thymol Menthol The above menthol compoundproduct contains three asymmetric carbon atoms and therefore, can existin four racemic modifications known as dl-menthol, dl-isomenthol,dl-neomenthol and dl-neoisomenthol. The graphic formulas for thesecompounds are:

9 H (3 H3 Q 3 0 a 0H OH OH OH d l-menthol dl-isom enthol dl-neomentholdl-neoisom ethol In these illustrations, the dotted lines refer togroups below the plane of the cyclohexane ring and the solid lines referto groups above the plane of the ring. As employed herein, the termisomenthol isomers is to be understood as referring to bothdl-isomenthol and dl-neoisomenthol.

When the oxidation of the above menthol compounds is carried out undercontrolled conditions, dl-menthol and dl-neomenthol give dl-menthonewhereas dl-isomenthol and dl-neoisomenthol give dl-isomenthone. Thisconversion is represented as follows:

0 H3 C H3 (ll-menthol dl-isomenthol an or and/or dl-neomenthol Odl-neoisomenthol 0 dl- 1- .menthone isomenthone.

Isomenthone, both in the optically active and racemic form is morehighly valued in the perfum industry than the dl-menthones and has beenfound to be an important constituent of geranium oil, a highly valuedessential oil.

2 Furthermore, the presence of isomenthone in synthetic ros and geraniumperfume compositions is known to'im:- part a pleasingly fragrantcharacter thereto. Accordingly, a satisfactory preparation ofisomenthone ishighly desirable and such preparation requires essentiallyareadily available source of the isomenthol isomer starting materials.Unfortunately, 'however, these particular menthol isomers have notheretofore been readily obtained by hydrogenating thymol. 1

The prior art'for the most part has indicated that the catalytichydrogenation of thymol gives mainly dl-menthol and dl-neomenthol.However, since much of the earlier work was carried out before thedevelopment of modern analytical techniques such as infraredspectroscopy or gas-liquid chromatography were developed, the exactcomposition of these menthol isomers is in doubt. Recent work may becited from Industrial and Engineering Chemistry (vol. 39, pp. 1150-4160,1947) where it is stated that hydrogenation of thymol in the presence ofa copperchromium catalyst gives 80% of menthol isomers and nickel onKieselguhr gives 56% menthols. The work of Huckel in Justus LiebigsAnnalen der Chemie (vol. 637, pp. 1-30, 1960) has shown that thehydrogenation of thymol in the presence of a copper chromite catalystgives 81.3% of menthol isomers and 18.7% of isomenthol isomers whereasRaney nickel catalyst gives 40.5% menthol isomers and 59.5% isomentholisomers; and Mohrs platinum catalyst gives 21% menthol isomers and 71%isomenthol isomers.

It has now been unexpctedly discovered, however, that the desiredisomenthol isomers may be produced as the principal product of thehydrogenation of thymol through the utilization of a cobalt catalystconsisting of either Raney cobalt or cobalt oxide. While the propertiesand characteristics of catalysts cannot always b predicted withcertainty nor their operation in any particular reaction readilyexplained, the remarkable activity of the Raney cobalt or cobalt oxidecatalysts to effect the principal production of isomenthol isomers inthe hydrogenation of thymol is most surprising and unexpected,especially in view of the fact that other cobalt containing catalysts donot exhibit a comparable level of activity.

Accordingly, it is an object of this invention to provide an improvedprocedure for preparing isomenthol isomers by hydrogenating thymol inthe presence of a cobalt catalyst consisting of either Raney cobalt orcobalt oxide. Another object of this invention is to prepare isomentholisomers in proportions not heretofore obtainable in the hydrogenation ofthymol with other catalysts and, moreover, at such a high level ofpurity that the isomenthol isomers obtained in the hydrogenation may bedirectly oxidized to the valuable isomenthone without extensivepurification. These and other objects and features of the presentinvention will appear from the following description thereof whereinreference is made to typical procedures and methods of'operation for thepurpose of indicating the nature of the invention but without intendingto limit the invention thereby.

The ready obtainment, in the hydrogenation of thymol, of a productcontaining mostly the isomenthol isomers is to be highly desired becausethe close boiling points of the menthol isomers renders separation byusual means, such as distillation, impractical. Even to obtain anenriched isomenthol fraction (75%) one suffers considerable loss ofisomenthol in the intermediate fractions. Enrichment of the isomentholisomers can be accompanied to a limited degree by fractionalrecrystallization of a solid derivative such as phthalate ester.However, this procedure results in considerable losses and is furthereconomically unattractive because of the necessity for subsequentlyregenerating the isomenthols from the phthalate or other derivative.

U The use of a Raney cobalt or cobalt oxide according to this inventionresults in the production of principally the isomenthol isomers and thusavoids these tedious and costly procedures for obtaining substantialquantities of the isomenthol isomers. However, in addition to thishighly desirable result, the isomenthol isomer hydrogenation product isso pure that it,can be oxidized directly to obtain a product which mayhave an isomenthone content of more than 90%; a quality of isomenthonenot, previously available.

In using Raney cobalt or cobalt oxide to effect the hydrogenation ofthymol, we have found that a product is obtained containingapproximately 90% or more of the isomenthol isomers. The use of theRaney cobalt or cobalt oxide catalysts thus produce a highly selectivereduction of thymol, at a level which has not heretofore beenaccomplished with any of the well known hydrogenation catalysts.

The Raney cobalt or cobalt oxide catalysts utilized in the process ofthis invention are the commercially available forms. The Raney cobaltcatalyst of commerce is generally prepared by the alkali digestion of analuminum cobalt alloy. Of the two cobalt catalysts, the most desirableresults are generally obtained with the Raney cobalt and for thisreason, Raney cobalt is the preferred catalyst for use in the process ofthis invention. The amount of catalyst required is not critical and willdepend upon the conditions of temperature and hydrogen pressure underwhich the reaction is carried out. These conditions may be varied over aconsiderable range without unduly aifecting the reaction. However, ingeneral, and for most practical purposes, about to 50% by weight of thecobalt catalyst based on the weight of the thymol are employed and thepressures may range from about 100 to 1200 pounds per square inch whilethe temperatures may vary from about 80 C. to 200 C. The reaction isgenerally continued until the absorption of hydrogen has ceased or for aperiod of from about 2 to hours. Thus, a highly satisfactory reductionis obtained when thymol is hydrogenated in the presence of 10% by weightof Raney cobalt or cobalt oxide at a temperature of about 130 C. andunder a hydrogen pressure of about 100 to 500 p.s.i. In general, therate of reduction will decrease with decreasing amounts of catalyst andat lower temperatures and pressures without materially changing theamount of isomenthol isomers formed. For convenience in handling, wealso prefer to use a solvent for the thymol such as isopropanol,methanol, ethanol, dioxane, and the like. However, the use of a solventis not necessary for the success of the reaction.

In order to indicate typical procedures which may be followed in thepractice of the present invention, the following examples are cited.

EXAMPLE I A mixture of 75 gms. (0.5 mole) of commercial thymol, 33 gms.of Raney cobalt and 26 gms. of isopropanol was charged to an autoclaveequipped with a stirring device. Hydrogen was added until the totalpressure was approximately 900 p.s.i. and the mixture heated to about180 C. Three equivalents (1.5 moles) of hydrogen were absorbed inapproximately 3 hours, and then ceased. The autoclave was then cooled,the contents discharged, and the catalyst removed by filtration. Theproduct isolated by distillation of the filtrate amounted to 73 gms. ofB.P. 8l87 at 2 mm. This material solidifies to a crystalline mass onstanding. A gas liquid ch'romatograph of this solid on a Hyprose columnshowed it to contain 2.7% neomenthol, 9.8% neoisomenthol, 2.7% mentholand 84.7% isomenthod. The total isomenthol isomers amounted therefore to94.5%.

EXAMPLE II A mixture of 225 gms. (1.5 moles) of commercial thymol, 22.5gms. of Raney cobalt and 75 ml. of isopropanol 4 I. i 1 5'' gr) wascharged to an autoclave mounted on a' rocking' device. Hydrogen wasaddeduntil the total pressure was approximately 500 p.s.i. and themixture was heated to about 130 C. Three equivalents (4.5 moles) ofhydrogen were absorbed in approximately 6.25 hours, and then ceased. Theautoclave was then cooled, the contents discharged and the catalystremoved by filtration". The product isolated by distillation of thefiltrate amounted'to 218 gms. of B.P. -86 at 2 mm. This materialsolidified on standing. A gas-liquid chromatograph on a .Hyprose columnshowed it to contain 1.2% neomenthol,-11.7% neoisomenthol, 2.1% mentholand 85.0% isomenthol. The total isomenthol isomers amounted, therefore,to 96.7%.

EXAMPLE III A mixture of 75 gms. (0.5 mole) of commercial thymol, 33gms. of Raney cobalt and 26 ml. of isopropanol was charged to anautoclave. Hydrogen was added until the total pressure was 250 p.s.i.and the mixture heated to about After the hydrogenation was completed,the autoclave was cooled and the contents discharged and filtered.Analysis of the crude filtrate by gas-liquid chromatography on a Hyprosecolumn showed it to contain 3.7% neomenthol, 22.0% neoisomenthol, 3.3%menthol and 71.0% isomenthol. The total isomenthol isomers amounted,therefore, to 93.0%.

EXAMPLE IV A mixture of 225 gms. (1.5 moles) of commercial thymol, 22.5gms. of cobalt oxide catalyst and 75 ml. of isopropanel was charged toan autoclave mounted on a rocking device. Hydrogen was added until thetotal pressure was approximately 500 p.s.i. and the mixture was heatedto about C. Three equivalents (4.5 moles) of hydrogen was absorbed inapproximately 6 hours, and then ceased. The autoclave was then cooled,the contents discharged and the catalyst removed by filtration. Theproduct isolated by distillation of the filtrate amounted to 220 gms. ofB.P. 7984 at 1 mm. This material solidified to a crystalline mass onstanding. A gas-liquid chromatograph on a Hyprose column showed it tocontain 5.0% neomenthol, 10.7% neoisomenthol, 7.8% menthol and 76.5%isomenthol. The total isomenthol isomers amounted, therefore, to 87.2%.

EXAMPLE V A mixture of 75 gms. (0.5 mole) of commercial thymol and 7.5gms. of Raney cobalt was charged to an autoclave equipped with aplunging-type agitator. Hydrogen was added until the total pressure is300 p.s.i. and the mixture was heated to about C. Three equivalents ofhydrogen (1.5 moles) were absorbed in approximately 7.6 hours. Theautoclave was then cooled, the contents discharged and the catalystremoved by filtration. Analysis of the crude filtrate by gas-liquidchromatography on a Hyprose column showed it to contain 3.6% neomenthol,4.6% neoisomenthol, 5.7% menthol and 86.1% isomenthol. The totalisomenthol isomers amounted, therefore, to 90.7%.

EXAMPLE VI In this example, thymol was hydrogenated in the presence of acobalt catalyst other than either the Raney cobalt or cobalt oxidecatalysts of this invention. The following results obtained therewithmay be contrasted with those of Examples I to V to demonstrate theunusual activity of the Raney cobalt or cobalt oxide catalysts inpreparing isomenthol isomers in contrast to even other cobalt catalysts:

A mixture of 450 gms. (3.0 moles) of commercial thymol, 67.5 gms. of acommercially available cobalt catalyst (Harshaw Company, Cobalt-0104T),and 200 milliliters of isopropanol was charged to an autoclave mountedon a rocking device. Hydrogen was added until the total pressure wasapproximately 500 p.s.i. and the mixture was heated to about 150 C.Three equivalents (9.0 moles) of hydrogen were absorbed in approximately23 hours. The autoclave was cooled, the contents discharged and thecatalyst removed by filtration. Analysis of the crude filtrate by gasliquid chromatography on a Hyprose column showed it to contain 6.3%neomenthol, 5.2% neoisomenthol, 17.2% menthol and 71.5% isomenthol. Thetotal isomenthol isomers amounted, therefore, to 76.7%.

It will be apparent from the foregoing examples that the temperatures,pressures and duration of the hydrogenation treatment can be variedconsiderably. In view thereof, it should be understood that theparticular procedures represented by the examples cited are intended tobe illustrative only and are not intended to limit the scope of theinvention.

We claim as our invention:

1. A process for producing a product containing approximately 90 percentof isomenthol isomers which cornprises hydrogenating thymol in thepresence of Raney cobalt catalyst, said cobalt catalyst being present inan amount of from about 5 to 50 weight percent based upon the weight ofthymol, at a temperature of from about 80 to 200 C. and a pressure offrom about 100 to 1200 pounds per square inch, and recovering theproduct.

2. A process for producing a product containing approximately 90 percentof isomenthol isomers which comprises hydrogenating thymol in thepresence of Raney cobalt catalyst, said catalyst being present in anamount of from about 5 to weight percent based upon the weight ofthymol, at a temperature of from about to C. and a pressure of fromabout 250 to 900 pounds per square inch, and recovering the product.

References Cited UNITED STATES PATENTS 1,247,629 11/ 1917 Brochet.

1,625,771 4/ 1927 Schollkopf. 2,790,835 4/ 1957 Peppratt et al.2,927,140 3/1960 Kaarsemaker et al.

OTHER REFERENCES BERNARD HELFIN, Primary Examiner.

H. MARS, Assistant Examiner.

1. A PROCESS FOR PRODUCING A PRODUCT CONTAINING APPROXIMATELY 90 PERCENTOF ISOMENTHOL ISOMERS WHICH COMPRISES HYDROGENATING THYMOL IN THEPRESENCE OF RANEY COBALT CATALYST, SAID COBALT CATALYST BEING PRESENT INAN AMOUNT OF FROM ABOUT 5 TO 50 WEIGHT PERCENT BASED UPON THE WEIGHT OFTHYMOL, AT A TEMPERATURE OF FROM ABOUT 80* TO 200*C. AND A PRESSURE OFFROM ABOUT 100 TO 1200 POUNDS PER SQUARE INCH, AND RECOVERING THEPRODUCT.